Studies are being performed on the relationship of the energy status of the hippocampal slice to synaptic transmission in the region of the dentate gyrus. Creatine was added to the incubation medium for varying periods of time and the accumulation of P-creatine and ATP were determined. While the levels of ATP did not change over a 5 hour incubation, the concentration of P-creatine increased by 4- and 6-fold at 3 and 5 hours of incubation, respectively. The perforant pathway axons were stimulated and the activity recorded in the region of the dentate gyrus. The loss of the signal during anoxia was delayed in those slices incubated with creatine which suggests a relationship between synaptic transmission and energy status of the tissue. In certain neurological disorders, enlarging the energy reserves of the brain might prevent or minimize the deficits induced by the insults. However, attempts to elevate P-creatine by injection of creatine into the ventricles of the brain have generally failed. Therefore, the characteristics of the creatine-induced increase in P-creatine in braine slices is being examined. Preliminary data suggest that the availability of phosphate may be important to the generation of P-creatine. Naloxone has been shown to reverse many of the behavioral effects resulting from brain ischemia. The level of analgesia was determined in bilaterally ischemia gerbils and found to be significantly higher than in control gerbils. This effect was reversed by the administration of 1 mg/kg (ip) of naloxone. In addition, the stereotypical behavior during ischemia was partially prevented. In spite of these changes, one criterion of ischemic injury, namely the loss of CA 1 neurons by 4 days of recirculation after 5 minutes of bilateral ischemia, was not altered by naloxone pretreatment. Studies including the measurement of endogenous opiates are underway to determine the nature of the naloxone effect.